Human Cytomegalovirus (HCMV), a DNA virus, is a human pathogen belonging to the family of Herpesviridae. Cytomegalovirus infection is widely present worldwide. Once infected by HCMV, human body will carry a latent virus for a lifetime, and the latent virus may be activated occasionally.
Most of HCMV infections are inapparent infections, but would result in serious or even lethal diseaeses in fetuses and immunocompromised populations. For example, if congenital CMV infection occurs in fetus (i.e., CMV passes through blood-placenta barrier and infects intrauterine fetus), it will result in serious clinical hazards, including fetal death, abortion, birth defects, and the like [1,2] (Dollard S C, Grosse S D, Ross D S. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol. 2007, 17: 355-363; Jiang Yi. Congenital cytomegalovirus infection: transmission from mother to infant and diagnosis. CHINESE JOURNAL OF NEONATOLOGY. 2009, 24:261-265). Most of studies show that CMV is a congenital infectious pathogen in neonate, which is the most common and the most harmful pathogen in the world, and the most important cause for sensorineural hearing loss and neural development retardation in children. In immunocompromised populations, such as organ transplant patients and AIDS patients, HCMV will activate infection and cause systemic complication.
Therefore, it is necessary to screen pregnant women susceptible to congenital CMV infection or immunosuppressed patients susceptible to human cytomegalovirus (HCMV) active infection, in order to employ intervention measures prior to occurrence of harmfulness.
Researchers believed in the past that antibody-negative pregnant mothers were susceptible to primary cytomegalovirus infection in pregnancy, and therefore it was quite possible to result in congenital infection in fetus [3,4] (Fowler K B, Stagno S, Pass R F, et al. The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med, 1992, 326: 663-667.2; Kenneson A, Cannon M J. Review and meta-analysis of the epidemiology of congenital cytomegalovirus infection. Rev Med Virol, 2007, 17: 253-276); the newborns delivered by antibody-positive pregnant mothers rarely had serious clinical outcomes. However, in recent years, the results of the systemic researches conducted in some developing countries where CMV is highly prevalent have gradually reversed this erroneous cognition. The results of these systemic researches demonstrates that most of the children with hearing disorder in developing countries are resulted from transmission from CMV antibody-positive mother to infant [5-7] (Manicklal S, Emery V C, Lazzarotto T, Boppana S B, Gupta R K. The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev. 2013, 26: 86-102; Mussi-Pinhata M M, Yamamoto A Y, Moura Brito R M, de Lima Isaac M, de Carvalho e Oliveira P F, Boppana S, Britt W J. Birth prevalence and natural history of congenital cytomegalovirus infection in a highly seroimmune population. Clin Infect Dis. 2009, 49:522-528; Yamamoto A Y, Mussi-Pinhata M M, Isaac Mde L, Amaral F R, Carvalheiro C G, Aragon D C, Manfredi A K, Boppana S B, Britt W J. Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population. Pediatr Infect Dis J. 2011, 30:1043-1046). Some studies show that intrauterine infection in the fetus of pregnant women who are seropositive for CMV prior to pregnancy is associated with maternal recurrent infection (also called “reactivation” or “reinfection”) by CMV during pregnancy [8,9] (Boppana S B, Rivera L B, Fowler K B, Mach M, Britt W J. Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N Engl J Med. 2001, 344: 1366-1371; Ross S A, Arora N, Novak Z, Fowler K B, Britt W J, Boppana S B. Cytomegalovirus reinfections in healthy seroimmune women. J Infect Dis. 2010, 201: 386-389). Now, CMV-IgM and IgG antibody assays are commonly used in various countries to determine prenatal CMV active infection in pregnant women. IgM and IgG antibody assays are of certain value for diagnosis of primary infection in antibody-negative pregnant women prior to pregnancy. However, when IgM and IgG antibody assays are used to diagnose reinfection in antibody-positive pregnant women prior to pregnancy, both the sensitity and specificity have been questioned a lot [10,11] (He Xiaozhou, Wang Xiaofang, Wang Shiwen; Research Progress in Congenital Cytomegalovirus Infection and Detection Method thereof. Chinese Journal of Virology. 2012, 28:73-77; Ross S A, Novak Z, Pati S, Boppana S B. Overview of the diagnosis of cytomegalovirus infection. Infect Disord Drug Targets. 2011, 11:466-474).
Therefore, there is need in this field to develop new methods with high sensitivity and specificity so as to accurately and effectively assess whether a subject is at risk of developing human cytomegalovirus (HCMV) active infection.